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PWD Immunizations–My Thoughts

Introduction

Puppy ImmunizationsThe common veterinary practice of annual repeat vaccinations of an animal has been challenged in the past decade as unnecessary and possibly harmful. Two reports in the late 1990s demonstrated that vaccinations could trigger autoimmune disease particularly hemolytic anemia. These references are given below. There is considerable recent scientific evidence that immunity persists for many years, perhaps even for life, from modified live virus vaccines given to a puppy or young adult. Immunity to a specific virus does not require an annual "booster", because the antibodies from the first vaccine administration will wipe out the vaccine virus, just as maternal antibody does. Because of the dramatic increase in canine autoimmune disease it makes no sense to introduce unnecessary antigen, adjuvant, and preservatives into your pet's immune system by administering booster vaccines.
Non-core bacterial vaccines against Lyme disease (Borrelia) and Bordetella do require boosters. A major turning point in challenging annual vaccinations was the statement of the American Veterinary Medical Association (AVMA) in September 2001 "unnecessary stimulation of the immune system does not result in enhanced disease resistance and may increase the risk of adverse post-vaccination events." The AVMA recommended that veterinarians create "core" and "non-core" vaccination programs … and that vaccine schedules be tailored to the needs of each specific animal. In 2006 the American Animal Hospital Association's Canine Vaccine Task Force changed their recommendation as well to a three-year schedule for modified live virus vaccines after a vaccine administered at one year of age. I would strongly encourage you to review the work of Dr Jean Dodds and Dr. Ron Schultz that is linked at the end of this article. These two no-nonsense veterinary scientists are the preeminent researchers in the field of vaccine science.

History

The term vaccination was coined by the English physician Edward Jenner in 1796. He derived the term from the Latin word for cow "vacca". This was based on his attempts to prevent smallpox in humans by inoculating them with cowpox (CPXV). Jenner had observed that milkmaids who developed cowpox (a mild skin infection in humans) from infected pustules on a cow's udder did not develop smallpox when exposed to the smallpox (vaccinia) virus.

Definitions

IMMUNITY:
The canine immune system begins to develop at approximately 45 days of fetal life and is complete by six months of age. There is some variability in this timing with large breeds requiring more time to develop a mature immune system than smaller breeds. Mammalian immune systems have evolved over tens of thousands of years mainly to protect the body from infection. A secondary function is to scan circulating cells for "self" versus "non-self" MHC (Major Histocompatibility) antigens. This The immune system is divided into two major components: the innate immune system and the adaptive immune system. The innate immune system is the initial defense mechanism. It developed long before the adaptive immune system and its responds nonspecifically but is ready to be mobilized upon the first signs of infection. The principal component is pattern recognition receptors (PRR) on cells of the innate immune system. These receptors recognize microbe-specific molecules that are called PAMPs: pathogen-associated molecular patterns. Mammalian PRRs have been further divided into two types: endocytic PRRs and signaling PRRs. Endocytic PRRs promote the attachment and destruction of microbes by circulating phagocytes. While signaling PRRs release important immune proteins such as cytokines. Toll-like receptors are membrane receptors responsible for the body's secretion of these powerful immune proteins that are important in the response to microbial invaders as well as in autoimmune disease. The adaptive immune system launches attacks specific to the invading pathogen and requires some time to tailor its custom-made response. The adaptive system "remembers" antigens it has encountered and reacts more quickly and efficiently the next time that antigen is found, yet more slowly than the innate system. This concept of "immunologic memory" is the reason behind all vaccinations. The adaptive system consists of humoral and cellular immunity.

HUMORAL IMMUNITY–IMMUNOGLOBULINS
Humoral immunity is mediated by secreted antibodies from the body's B-cell lymphocytes. These B-cells transform into plasma cells that make antibodies.Some B-cells revert to small lymphocytes, 'memory' cells, and the expanded clone of these cells, on re-exposure to the antigen, undergo further lymphocyte blastogenesis, leading to further increased antibody production and numbers of memory cells. This explains the rapid antibody response to a second exposure to an antigen. The glycoproteins secreted by transformed plasma cells are referred to as immunoglobulins. Mammalian species can make five types of immunoglobulin–IgA, IgD, IgE, IgG and IgM.

CELLULAR IMMUNITY
A better term would be cell-mediated immunity. This type of immunity does require antibodies or complement. It may have a greater importance than antibody response, particularly for some antigens such as viruses.It is dependent upon T lymphocytes which are sensitized by their first exposure to a specific antigen such as with a vaccination. With a second exposure to the antigen a clonal expansion of specifically reactive T lymphocytes including cytotoxic T lymphocytes (Tc lymphocytes) occurs. These T lymphocytes play a major role in eliminating the foreign antigen. Subsequent exposure They also release a group of substances known as lymphokines (interferon, interleukins) that can direct kill pathogens. Cellular immunity explains while animals with no detectable antibodies may be fully protected against a disease. T cells have also been implicated in both canine and human "autoimmune disease" that occurs when the T cells attack the body's own cells. This is certainly a reason not to overvaccinate and reactivate "memory" T cells.

PASSIVE IMMUNITY –MATERNAL DERIVED ANTIBODY
IGG antibody is routinely transferred by the placenta from the mother to all her fetuses. In addition, IGA in canine colostrum (milk produced in the first 48 hours) may be absorbed from a puppy's intestine after nursing. The amount of antibody transferred depends on the mother's own immune status as well as an individual puppy's ability to nurse. Usually these antibodies decline over time, but if present prevent a puppy from developing his/her natural immunity with early vaccinations.

ACTIVE IMMUNITY
Active immunity is long-term immunity. Once B cells and T cells are activated by initial exposure to a pathogen, memory B-cells and T- cells develop. These "memory" cells usually persist in the lymphatic system of the animal longterm. Active immunity can be acquired following infection or artificially acquired by vaccines, in a process called immunization. Active immunity involves both humoral immunity (B-cells) and cell-mediated immunity (T-cells).

GASTROINTESTINAL TRACT LOCAL IMMUNITY
Puppies are born with a completely sterile intestine. Over the next few weeks as they nurse and interact with their environment their intestinal tract will become colonized by various bacteria. We feel that maintaining beneficial bacteria in the gut is important in the immunologic development of a puppy. Direct-feed microbials (DFM) or probiotics Probiotics (a term coined in 1953 by Werner Kollath in contrast to antibiotics) are bacterially derived products introduced into the intestine orally to promote the growth of beneficial microorganisms. Two species of canine-specific probiotics, Bifidobacterium and Lactobacillus, have been studied the most. These two naturally occurring bacteria restore a natural balance of bacteria in the canine colon. Two major sources of probiotics are fermented products usually yogurt or kefir or canine-specific microbial live culture supplements such as Bene-Bac or Fastrack. We begin feeding active culture yogurt when weaning begins at 3-4 weeks.

VACCINES

A canine vaccine contains an antigen (a weakened live pathogen (virus/bacteria), part of a pathogen or a killed pathogen) that stimulates an immune reaction in the dog to protect against the same pathogen in the future.

CORE VACCINES

PARVOVIRUS (CPV-2): Canine parvovirus is a new virus that appeared in the United States in the mid 1970s. It is thought to have evolved from the feline panleukopenia virus (FPV) as a cross species infection. The virus continues to evolve as antigenically different virus types continue to be isolated. Current vaccines protect against CPV-2 both the A and B strains.

DISTEMPER (CDV): Canine distemper virus was first reported by Carre in 1905. This RNA virus is closely related to human measles virus and cattle rinderpest. It has a high mortality particularly in puppies less than 6 months of age. Killed virus vaccines were developed in the 1940s but did not protect the majority of dogs. Drs. James Baker and James Gillespie in the early 1960s recognized that maternal-derived antibodies prevented vaccinated puppies from developing active immunity. For this reason many puppies received human measles vaccines at 4-6 weeks and since they had no antibody to measles they were partially protected against the kindred distemper virus. THERE IS NO REASON NOW TO GIVE MEASLES VACCINE TO A PUPPY. Modified (attenuated) live virus distemper vaccines were also introduced. Current distemper vaccines are called "high-titer" and are effective in inducing active immunity in 99% of puppies if given in 3 doses four weeks a part beginning at 6-8 weeks. It is extremely important that the last vaccine be given at 16 weeks.

CANINE ADENOVIRUS 2 (CAV-2)(CAV-1 INFECTIOUS HEPATITIS):
Canine adenovirus type 2 causes respiratory disease in dogs and is one of the infectious agents commonly associated with canine infectious tracheobronchitis, which is commonly called "kennel cough". Bordetella and parainfluenza also cause "kennel cough" so even if your puppy has received CAV-2 vaccination he/she will still require Bordetella protection. The CAV-2 vaccine also crossprotects against infection with canine adenovirus type 1 (CAV-1). CAV-1 causes infectious canine hepatitis - a dangerous and potentially fatal infection. This is the reason it is administered with the other core vaccines.

RABIES Rabies virus infects the central nervous system of mammals and leads to eventual death. The virus is almost always acquired from the bite of a rabid animal. Rabies vaccine is the only immunization required by law in all 50 states and U.S. territories. This requirement is primarily to prevent humans from contracting rabies from dog bites. The Centers for Disease Control and Prevention (CDC) maintains records for all rabies cases reported in 49 states (Hawaii is rabies free) and Puerto Rico. In 2009 the last year with complete statistics 6,690 cases of rabies in animals were reported. 92% of the cases occurred in wild animals with 8% in domestic animals. 81 cases (1.2%) were reported in dogs in the United States. No cases of canine rabies were reported in California. Bats and skunks were responsible for 186/227 cases reported in California. No case of rabies occurred in a domestic animal in California in 2009. Significantly in the 31 cases of human rabies in the United States occurring between the years 2000-2009, seven were due to dog bites and all the bites occurred in a foreign country (Ghana, Haiti, El Salvador, India, Philippines {2}) or Puerto Rico (1). Current rabies vaccines are labeled as one or three year vaccines. However they are basically the same vaccines with different follow-up required for their biologic license. California law requires initial rabies vaccination for all puppies by 4 months of age. A second vaccination is required a year later (16 months). It is required by law to revaccinate every 3 years thereafter.

CANINE INFECTIOUS TRACHEOBRONCHITIS Infectious tracheobronchitis (kennel cough) is a complex clinical infection caused by a number of respiratory pathogens that can infect dogs alone or in combination. Causative viruses include distemper (CDV), adenovirus (CAV-2)-detailed above, parainfluenza virus (CPIV), herpesvirus (CHV), and reoviruses. Bordetella bronchiseptica is a causative bacterial pathogen. The performance of injectable ITB vaccines is quite different from that of intranasally administered vaccine. The injectable vaccine for ITB provides duration of immunity of up to 7 months or longer depending on the antigen. It is not known whether parenteral administration of ITB antigens culminates in the development of an effective local (upper respiratory tract) immune response. Intranasal administration can be administered as early as 3 weeks of age (depending on the product), appears to induce a local immune response in the upper airway that is not interfered with by maternal antibody, and has a relatively rapid onset (3 to 5 days).

Titers

The current fad is the use of antibody titers in adult dogs to see if revaccination is indicated. Detection of antibody to a specific pathogen (virus or bacteria) indicates only prior vaccination or exposure to the disease. A titer is performed by diluting an animal's blood to measure the amount of antibody in the blood to a specific virus/bacteria. For example, a parvo titer measures the amount of antibody against parvovirus that a dog has in his/her blood. Prior studies in dogs are used to ascertain a level of antibody that protects against that disease. This level is called a "protective titer." However a low titer does not mean a lack of protection. This is especially true if the titer is measured many years after the initial vaccinations. It is impossible to tell whether a specific level of antibody will protect an individual animal from developing a disease after exposure to an organism. Remember antibody titers only assess one half of the individual animal's immune system–immunoglobulin levels. Cellular immunity is not evaluated by antibody titers. Small series have shown that animals with an antibody titer of zero did not develop a disease when exposed to the live virus responsible for the disease.
Dr. Richard Ford, of North Carolina State University, states, "The risk lies in the fact that a single serum sample divided three times and sent to three different laboratories is quite likely to yield three different titers, and quite possibly three different interpretations. What may be deemed 'protective' by one laboratory could well be labeled 'susceptible' by another. Furthermore, it is important to note that a vaccinated dog that does not have a significant concentration of antibody may, in fact, have excellent immunity. A 'negative' antibody titer does not necessarily correlate with susceptibility to infection. Likewise, the presence of antibody, even at high levels, does not guarantee immunity subsequent to exposure." Vaccine producers are required as a proof of efficacy to demonstrate protection against a disease by challenging animals previously vaccinated with their vaccine by exposing them to the active pathogen. Vaccine manufacturers are not required to demonstrate long-term protection and it is not in their economic interest to research the length of protection. Current revaccination protocols are merely an educated guess and have been modified over time. My personal study has led to believe that the current titers available from commercial labs are worthless for adult dogs. The only use I see for titers is to design a minimal vaccination protocol for a puppy or to see if an adult dog has an unknown vaccination history.

Rationale for a Series of Puppy Immunizations

Immunity TimingMany clients ask "Why do we give puppies all these shots?" The reason is that the passive transferred immunity that all puppies get from their mother i.e. Maternal Derived Antibiotics disappear at an unpredictable rate over the first four months of a puppy's life. Interesting the disppearance of maternal antibodies to each specific disease also varies. Active immunity to any vaccine will only occur when the individual puppy's maternal derived antibody is no longer present. This is the reason that we usually use a 7 week, 10 week, 13 week and 16 week schedule for any puppy we keep. The illustration at the right shows the rationale for this approach. If an immunization is given at 16 weeks of life there is a 99% chance that the puppy will develop active immunity to the disease he/she is being vaccinated against.
Note that titers" done 4 weeks after a series of puppy immunizations show that a rare puppy is a "non-responder" i.e. this varies by the virus 1/1000 for parvo and 1/5000 for distemper and adenovirus 2. The reasons that vaccination fails to provoke immunity are usually related to the use of improperly stored, handled, or administered vaccines. Very rarely, the puppy has a defective immune system and is not capable of developing active immunity.

Current Recommendations

We believe that we have been overvaccinating our dogs and the best recommendation is to use the protocol recommended by Dr. Ron Schultz, the veterinary immunologist at the University of Wisconsin:

All puppies should have core vaccinations against distemper, parvo and adenovirus 2 using modified live virus vaccines. How this is achieved will depend on your veterinarian particular schedule of puppy immunizations.
In accordance with current California state law, we recommend that puppies receive a single dose of killed rabies vaccine at 4 months of age. A booster is required one year later, and thereafter, rabies vaccination should be performed every 3 years with a vaccine approved for 3 year administration.

PLEASE NOTE THAT THESE RECOMMENDATIONS REGARDING RABIES VACCINATIONS ARE BASED ON THE LAW NOT IMMUNITY TO RABIES.

Other Vaccines

There are several non-core vaccinations that your older puppy may need these include leptospirosis, Lyme disease and rattlesnake bite. Your individual living situation and lifestyle will determine whether your puppy will require these particular immunizations. You should discuss the possible needs for these vaccinations with your veterinarian.

Disclaimer

I am a physician not a veterinarian. The information above is provided for information purposes only, and is not intended as a substitute for advice from a qualified veterinary health practitioner. All my recommendations are based on the best scientific evidence in 2012. However you need to make your own judgment about the risk/benefit ratio for other revaccinations.

References

1. Duval D, Giger U. Vaccine-induced immune-mediated hemolytic anemia in the dog. J Vet Intern Med 1996.
2. Hogenesch H, et al. Vaccine-induce autoimmunity in the dog. In: Schultz RD, ed. Advances in Veterinary Medicine 41: Veterinary Vaccines and Diagnostics. San Diego: Academic Press, 1999; 715-732

Links

Dr Jean Dodds 2011 Limited Vaccine Protocol
Dr Ron Schultz 2007 Vaccine Article